Genetic and Metabolic Disorders US Medical PG Practice Questions and MCQs
Practice US Medical PG questions for Genetic and Metabolic Disorders. These multiple choice questions (MCQs) cover important concepts and help you prepare for your exams.
Genetic and Metabolic Disorders US Medical PG Question 1: A 28-year-old woman comes to the physician for genetic counseling prior to conception. For the past year, she has had intermittent episodes of headache, nausea, abdominal pain, and tingling of her fingers. She also complains of dark urine during the episodes. Her mother and maternal uncle have similar symptoms and her father is healthy. Her husband is healthy and there is no history of serious illness in his family. Serum studies show elevated concentrations of porphobilinogen and δ-aminolevulinic acid. What is the probability of this patient having a child with the same disease as her?
- A. 25%
- B. 67%
- C. 50% (Correct Answer)
- D. 100%
Genetic and Metabolic Disorders Explanation: ***50%***
- This patient's symptoms (headache, nausea, abdominal pain, tingling, dark urine) and elevated **porphobilinogen** and **δ-aminolevulinic acid** are highly suggestive of **Acute Intermittent Porphyria** (AIP).
- AIP is an **autosomal dominant** disorder. Therefore, there is a **50% chance** that any child of an affected parent will inherit the disease-causing allele.
- Since her husband is healthy with no family history, he does not carry the mutation, making this a straightforward autosomal dominant inheritance calculation.
*25%*
- This probability would be expected in an **autosomal recessive** inheritance pattern when two carrier parents have a child, which is not the case here.
- It would also be the probability for an X-linked recessive disorder if the mother is a carrier and the father is unaffected, and they are discussing a son's inheritance.
- The clinical presentation and family history (mother and maternal uncle affected, consistent with autosomal dominant pattern) rule out this probability.
*67%*
- This probability is seen in specific genetic scenarios, such as the chance of a phenotypically normal sibling of an individual with an autosomal recessive disease being a carrier.
- It's not a standard probability for direct offspring of an affected individual with an autosomal dominant condition.
- This does not apply to the straightforward inheritance question being asked here.
*100%*
- This probability would occur if the disease were inherited in an **autosomal dominant** manner and the affected parent was **homozygous dominant** for the mutation.
- However, this is extremely rare in AIP, as most affected individuals are **heterozygous**.
- The family history pattern (affected mother with unaffected father having an affected child) is consistent with heterozygosity, not homozygosity.
Genetic and Metabolic Disorders US Medical PG Question 2: A 25-year-old man with a genetic disorder presents for genetic counseling because he is concerned about the risk that any children he has will have the same disease as himself. Specifically, since childhood he has had difficulty breathing requiring bronchodilators, inhaled corticosteroids, and chest physiotherapy. He has also had diarrhea and malabsorption requiring enzyme replacement therapy. If his wife comes from a population where 1 in 10,000 people are affected by this same disorder, which of the following best represents the likelihood a child would be affected as well?
- A. 0.01%
- B. 2%
- C. 0.5%
- D. 1% (Correct Answer)
- E. 50%
Genetic and Metabolic Disorders Explanation: ***Correct Option: 1%***
- The patient's symptoms (difficulty breathing requiring bronchodilators, inhaled corticosteroids, and chest physiotherapy; diarrhea and malabsorption requiring enzyme replacement therapy) are classic for **cystic fibrosis (CF)**, an **autosomal recessive disorder**.
- For an autosomal recessive disorder with a prevalence of 1 in 10,000 in the general population, **q² = 1/10,000**, so **q = 1/100 = 0.01**. The carrier frequency **(2pq)** is approximately **2q = 2 × (1/100) = 1/50 = 0.02**.
- The affected man is **homozygous recessive (aa)** and will always pass on the recessive allele. His wife has a **1/50 chance of being a carrier (Aa)**. If she is a carrier, she has a **1/2 chance of passing on the recessive allele**.
- Therefore, the probability of an affected child = **(Probability wife is a carrier) × (Probability wife passes recessive allele) = 1/50 × 1/2 = 1/100 = 1%**.
*Incorrect Option: 0.01%*
- This percentage is too low and does not correctly account for the carrier frequency in the population and the probability of transmission from a carrier mother.
*Incorrect Option: 2%*
- This represents approximately the carrier frequency (1/50 ≈ 2%), but does not account for the additional 1/2 probability that a carrier mother would pass on the recessive allele.
*Incorrect Option: 0.5%*
- This value would be correct if the carrier frequency were 1/100 instead of 1/50, which does not match the given population prevalence.
*Incorrect Option: 50%*
- **50%** would be the risk if both parents were carriers of an autosomal recessive disorder (1/4 chance = 25% for affected, but if we know one parent passes the allele, conditional probability changes). More accurately, 50% would apply if the disorder were **autosomal dominant** with one affected parent, which is not the case here.
Genetic and Metabolic Disorders US Medical PG Question 3: A 30-year-old man is brought into the emergency room for complaints of acute onset chest pain and shortness of breath. He has a history of mental retardation and lives at home with his adoptive parents. His parents inform you that he has not seen a doctor since he was adopted as child and that he currently takes no medications. The patient's temperature is 99.1°F (37.3°C), pulse is 108/min, blood pressure is 125/70 mmHg, respirations are 25/min, and oxygen saturation is 92% on 2L nasal cannula. Physical exam is notable for a tall, thin individual with high-arched feet and mild pectus excavatum. There is mild asymmetry in the lower extremities with discomfort to dorsiflexion of the larger leg. Lung auscultation reveals no abnormalities. What is the most appropriate next step in management?
- A. Chest radiograph
- B. Serum blood test
- C. Genetic testing
- D. Angiogram
- E. Electrocardiogram (Correct Answer)
Genetic and Metabolic Disorders Explanation: ***Correct: Electrocardiogram***
- **Acute chest pain** mandates an immediate **ECG** as the first diagnostic test to rule out **ST-elevation myocardial infarction (STEMI)**, which requires emergent intervention (PCI or thrombolysis).
- While this patient's presentation is highly suspicious for **pulmonary embolism (PE)** given the **unilateral leg swelling with pain on dorsiflexion** (suggestive of DVT), **tachycardia**, **tachypnea**, and **hypoxemia**, the ECG remains the most appropriate initial step per ACLS protocols for chest pain.
- ECG can also show findings suggestive of PE (sinus tachycardia, S1Q3T3 pattern, right heart strain) and help differentiate cardiac from pulmonary etiologies.
- The **Marfanoid features** (tall, thin, pectus excavatum, high-arched feet) raise concern for **aortic dissection**, which ECG can help evaluate alongside clinical assessment.
*Incorrect: Chest radiograph*
- Chest X-ray is critical in the workup and would typically be ordered simultaneously with or immediately after ECG in this patient with suspected PE.
- CXR helps exclude pneumothorax, pneumonia, and can show classic PE findings (Westermark sign, Hampton's hump), though it is often normal in PE.
- In the context of Marfan syndrome, CXR can reveal a widened mediastinum suggesting aortic dissection.
- However, ECG takes precedence as the immediate first step for any acute chest pain presentation.
*Incorrect: Serum blood test*
- Laboratory tests including **cardiac troponins** (for MI), **D-dimer** (for PE), and **CBC** are important but take time to result.
- D-dimer would be useful in this moderate-to-high probability PE case, but imaging (CT pulmonary angiography) would be more appropriate given the high clinical suspicion.
- Blood tests do not provide the immediate actionable information needed as the first diagnostic step in acute chest pain.
*Incorrect: Genetic testing*
- While the patient's phenotype suggests **Marfan syndrome** or another connective tissue disorder, genetic testing is an outpatient diagnostic tool for long-term management.
- It provides no immediate utility in the acute management of chest pain and respiratory distress.
- Genetic counseling and testing would be appropriate after stabilization and initial workup.
*Incorrect: Angiogram*
- **CT pulmonary angiography** would be the definitive test for PE diagnosis after initial ECG and CXR, but is not the immediate first step.
- **Cardiac catheterization** would be indicated if ECG showed STEMI or if there was high suspicion for ACS after initial workup.
- **CT aortography** might be needed if aortic dissection is suspected based on initial findings.
- Angiography is an invasive or advanced imaging procedure performed after non-invasive screening tests guide the diagnosis.
Genetic and Metabolic Disorders US Medical PG Question 4: A deficiency in which of the following lysosomal enzymes is inherited in a pattern similar to a deficiency of iduronate sulfatase (Hunter syndrome)?
- A. Sphingomyelinase
- B. Glucocerebrosidase
- C. Galactocerebrosidase
- D. Alpha-L-iduronidase
- E. Alpha-galactosidase A (Correct Answer)
Genetic and Metabolic Disorders Explanation: ***Alpha-galactosidase A***
- A deficiency in **alpha-galactosidase A** causes **Fabry disease**, which, like Hunter syndrome (iduronate sulfatase deficiency), is inherited in an **X-linked recessive** pattern.
- Both conditions primarily affect males, with carrier females potentially exhibiting milder symptoms.
*Sphingomyelinase*
- A deficiency in sphingomyelinase leads to **Niemann-Pick disease types A and B**, which are inherited in an **autosomal recessive** pattern.
- This mode of inheritance differs from the X-linked pattern of Hunter syndrome.
*Glucocerebrosidase*
- A deficiency in glucocerebrosidase causes **Gaucher disease**, inherited in an **autosomal recessive** pattern.
- This is a common lysosomal storage disorder, but its inheritance pattern is distinct from X-linked disorders.
*Galactocerebrosidase*
- A deficiency in galactocerebrosidase causes **Krabbe disease (globoid cell leukodystrophy)**, which is inherited in an **autosomal recessive** pattern.
- Krabbe disease is a severe neurodegenerative disorder, but its genetic transmission is not X-linked.
*Alpha-L-iduronidase*
- A deficiency in **alpha-L-iduronidase** causes **Hurler syndrome (MPS I)**, which is inherited in an **autosomal recessive** pattern.
- While both Hunter and Hurler syndromes are mucopolysaccharidoses, their genetic inheritance patterns are different.
Genetic and Metabolic Disorders US Medical PG Question 5: A 9-year-old boy is brought to the physician because his parents are concerned that he has been unable to keep up with his classmates at school. He is at the 4th percentile for height and at the 15th percentile for weight. Physical examination shows dysmorphic facial features. Psychologic testing shows impaired intellectual and adaptive functions. Genetic analysis shows a deletion of the long arm of chromosome 7. Which of the following is the most likely additional finding in this patient?
- A. Absent thymus gland
- B. Supravalvular aortic stenosis (Correct Answer)
- C. Brushfield spots on the iris
- D. Testicular enlargement
- E. Hand flapping movements
Genetic and Metabolic Disorders Explanation: ***Supravalvular aortic stenosis***
- The clinical presentation, including **dysmorphic facial features**, **growth restriction**, and **intellectual disability**, coupled with a **deletion on the long arm of chromosome 7**, is highly suggestive of **Williams syndrome**.
- **Supravalvular aortic stenosis** is a classic cardiovascular finding in **Williams syndrome**, present in about 75% of affected individuals.
*Absent thymus gland*
- An absent thymus gland is characteristic of **DiGeorge syndrome**, which is caused by a **deletion on chromosome 22q11**.
- This patient's genetic analysis indicates a deletion on **chromosome 7**, not chromosome 22.
*Brushfield spots on the iris*
- **Brushfield spots** are characteristic of **Down syndrome** (**trisomy 21**).
- The genetic finding of a **deletion on chromosome 7** rules out Down syndrome as the underlying cause.
*Testicular enlargement*
- **Testicular enlargement** is a hallmark feature of **Fragile X syndrome**, a genetic condition caused by an **FMR1 gene mutation** on the X chromosome.
- This patient's symptoms and genetic findings of a **chromosome 7 deletion** are not consistent with Fragile X syndrome.
*Hand flapping movements*
- **Hand flapping** is a common repetitive behavior observed in individuals with **autism spectrum disorder** and is also seen in some other genetic conditions like **Rett syndrome**.
- While individuals with Williams syndrome may have unique behavioral profiles, hand flapping is not a specific or typical feature of the syndrome, and the genetic finding points to Williams syndrome.
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